rs139912214
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001048166.1(STIL):āc.1455G>Cā(p.Leu485Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,614,076 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_001048166.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STIL | NM_001048166.1 | c.1455G>C | p.Leu485Phe | missense_variant | 12/17 | ENST00000371877.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STIL | ENST00000371877.8 | c.1455G>C | p.Leu485Phe | missense_variant | 12/17 | 1 | NM_001048166.1 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.00193 AC: 293AN: 152130Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00219 AC: 551AN: 251306Hom.: 4 AF XY: 0.00215 AC XY: 292AN XY: 135816
GnomAD4 exome AF: 0.00209 AC: 3056AN: 1461828Hom.: 5 Cov.: 32 AF XY: 0.00210 AC XY: 1525AN XY: 727206
GnomAD4 genome ? AF: 0.00192 AC: 293AN: 152248Hom.: 1 Cov.: 32 AF XY: 0.00201 AC XY: 150AN XY: 74444
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 02, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 26, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2024 | The p.Leu438Phe variant in STIL is classified as likely benign because it has been identified in 0.9% (267/29604) of Ashkenazi Jewish chromosomes, 0.4% (29/6060) of Middle Eastern chromosomes and 0.3% (156/60012) of Admixed American chromosomes, including 6 total homozygotes by gnomAD (http://gnomad.broadinstitute.org, v.4.0.0). In addition, computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1, BP4. - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 19, 2015 | - - |
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | STIL: BP4, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 08, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 17, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
Abnormal brain morphology Pathogenic:1
Likely pathogenic, flagged submission | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2013 | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Microcephaly 7, primary, autosomal recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at